Migrastatin (1) is a 14-membered ring macrolide natural product, that was first isolated from a cultured broth of Steptomyces sp. MK929-43F1 by Imoto et al. (see, Nakae et al., J. Antibiot., 2000, 53, 1130-1136; and Nakae et al., J. Antibiot., 2000, 53, 1228-1230). It was recently reported that cultures of Steptomyces platensis also produce Migrastatin (1a) and a related 12-membered ring macrolide compound, isomigrastatin (1b) (see, Woo et al., J. Antibiot., 2002, 55, 141-146).

Migrastatin has been shown to inhibit both migration and anchorage-independent growth of human tumor cells (see, Nakae et al., J. Antibiot., 2001, 54, 1104-1107), and has sparked interest in the area of cancer research. Specifically, migration of tumor cells is part of the complex process of metastasis, which is the leading cause of death in cancer patients. Therefore, Migrastatin and analogs thereof, including 12-membered ring macrolide isomigrastatin analogs, hold great potential as therapeutic agents for the treatment of cancer.
To date, access to isomigrastatin has only been possible by fermentation techniques. Clearly, there remains a need for isomigrastatin analogs. Therefore, there is a need to develop synthetic methodologies to access a variety of novel analogues of isomigrastatin, particularly those that are inaccessible by making modifications to the natural product. It would also be of particular interest to develop novel compounds that exhibit a favorable therapeutic profile in vivo (e.g., are safe and effective).